A phase I dose escalation and expansion trial of the next-generation oral SERD camizestrant in women with ER-positive, HER2-negative advanced breast cancer: SERENA-1 monotherapy results

• DOI: 10.1016/j.annonc.2024.04.012
• Publication Date: 2024-05-08T16:26:47Z
• Authors: E. Hamilton; M. Oliveira; N. Turner; J. García-Corbacho; C. Hernando; E.M. Ciruelos; P. Kabos; M. Ruiz-Borrego; A. Armstrong; M.R. Patel; C. Vaklavas; C. Twelves; V. Boni; J. Incorvati; T. Brier; L. Gibbons; T. Klinowska; J.P.O. Lindemann; C.J. Morrow; A. Sykes; R.D. Baird
• Keywords: Tolerability; Fulvestrant

Background SERENA-1 (NCT03616587) is a Phase 1, multi-part, open-label study of camizestrant in pre- and post-menopausal women with ER+, HER2− advanced breast cancer. Parts A B aim to determine the safety tolerability monotherapy define doses for clinical evaluation. Patients Methods Women aged 18 years or older metastatic recurrent cancer, refractory (or intolerant) therapy were assigned 25 mg up 450 once daily (QD; escalation) 75, 150, 300 QD (expansion). Safety tolerability, anti-tumor efficacy, pharmacokinetics, impact on ESR1m circulating tumor (ct)DNA levels assessed. Results By 9 March 2021, 108 patients received at 25–450 doses. Of these, 93 (86.1%) experienced treatment-related adverse events (TRAEs), 82.4% which grade 1 2. The most common TRAEs visual effects (56%), (sinus) bradycardia (44%), fatigue (26%), nausea (15%). There no 3 higher, serious (TRSAEs) ≤150 mg. Median tmax was achieved ∼2–4 hours post-dose all investigated, an estimated half-life 20–23 hours. Efficacy observed including prior CDK4/6 inhibitor and/or fulvestrant treatment, without baseline ESR1 mutations, visceral disease, liver metastases. Conclusions Camizestrant next-generation oral SERD pure ER antagonist tolerable profile. pharmacokinetics profile supports once-daily dosing, evidence pharmacodynamic efficacy heavily pre-treated patients, regardless ESR1m. This established 150 2 testing (SERENA-2, NCT04214288 SERENA-3, NCT04588298).